Cargando…

Transient Loss of Protection Afforded by a Live Attenuated Non-typhoidal Salmonella Vaccine in Mice Co-infected with Malaria

In immunocompetent individuals, non-typhoidal Salmonella serovars (NTS) are associated with gastroenteritis, however, there is currently an epidemic of NTS bloodstream infections in sub-Saharan Africa. Plasmodium falciparum malaria is an important risk factor for invasive NTS bloodstream in African...

Descripción completa

Detalles Bibliográficos
Autores principales: Mooney, Jason P., Lee, Seung-Joo, Lokken, Kristen L., Nanton, Minelva R., Nuccio, Sean-Paul, McSorley, Stephen J., Tsolis, Renée M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569369/
https://www.ncbi.nlm.nih.gov/pubmed/26366739
http://dx.doi.org/10.1371/journal.pntd.0004027
_version_ 1782390032814833664
author Mooney, Jason P.
Lee, Seung-Joo
Lokken, Kristen L.
Nanton, Minelva R.
Nuccio, Sean-Paul
McSorley, Stephen J.
Tsolis, Renée M.
author_facet Mooney, Jason P.
Lee, Seung-Joo
Lokken, Kristen L.
Nanton, Minelva R.
Nuccio, Sean-Paul
McSorley, Stephen J.
Tsolis, Renée M.
author_sort Mooney, Jason P.
collection PubMed
description In immunocompetent individuals, non-typhoidal Salmonella serovars (NTS) are associated with gastroenteritis, however, there is currently an epidemic of NTS bloodstream infections in sub-Saharan Africa. Plasmodium falciparum malaria is an important risk factor for invasive NTS bloodstream in African children. Here we investigated whether a live, attenuated Salmonella vaccine could be protective in mice, in the setting of concurrent malaria. Surprisingly, mice acutely infected with the nonlethal malaria parasite Plasmodium yoelii 17XNL exhibited a profound loss of protective immunity to NTS, but vaccine-mediated protection was restored after resolution of malaria. Absence of protective immunity during acute malaria correlated with maintenance of antibodies to NTS, but a marked reduction in effector capability of Salmonella-specific CD4 and CD8 T cells. Further, increased expression of the inhibitory molecule PD1 was identified on memory CD4 T cells induced by vaccination. Blockade of IL-10 restored protection against S. Typhimurium, without restoring CD4 T cell effector function. Simultaneous blockade of CTLA-4, LAG3, and PDL1 restored IFN-γ production by vaccine-induced memory CD4 T cells but was not sufficient to restore protection. Together, these data demonstrate that malaria parasite infection induces a temporary loss of an established adaptive immune response via multiple mechanisms, and suggest that in the setting of acute malaria, protection against NTS mediated by live vaccines may be interrupted.
format Online
Article
Text
id pubmed-4569369
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-45693692015-09-18 Transient Loss of Protection Afforded by a Live Attenuated Non-typhoidal Salmonella Vaccine in Mice Co-infected with Malaria Mooney, Jason P. Lee, Seung-Joo Lokken, Kristen L. Nanton, Minelva R. Nuccio, Sean-Paul McSorley, Stephen J. Tsolis, Renée M. PLoS Negl Trop Dis Research Article In immunocompetent individuals, non-typhoidal Salmonella serovars (NTS) are associated with gastroenteritis, however, there is currently an epidemic of NTS bloodstream infections in sub-Saharan Africa. Plasmodium falciparum malaria is an important risk factor for invasive NTS bloodstream in African children. Here we investigated whether a live, attenuated Salmonella vaccine could be protective in mice, in the setting of concurrent malaria. Surprisingly, mice acutely infected with the nonlethal malaria parasite Plasmodium yoelii 17XNL exhibited a profound loss of protective immunity to NTS, but vaccine-mediated protection was restored after resolution of malaria. Absence of protective immunity during acute malaria correlated with maintenance of antibodies to NTS, but a marked reduction in effector capability of Salmonella-specific CD4 and CD8 T cells. Further, increased expression of the inhibitory molecule PD1 was identified on memory CD4 T cells induced by vaccination. Blockade of IL-10 restored protection against S. Typhimurium, without restoring CD4 T cell effector function. Simultaneous blockade of CTLA-4, LAG3, and PDL1 restored IFN-γ production by vaccine-induced memory CD4 T cells but was not sufficient to restore protection. Together, these data demonstrate that malaria parasite infection induces a temporary loss of an established adaptive immune response via multiple mechanisms, and suggest that in the setting of acute malaria, protection against NTS mediated by live vaccines may be interrupted. Public Library of Science 2015-09-14 /pmc/articles/PMC4569369/ /pubmed/26366739 http://dx.doi.org/10.1371/journal.pntd.0004027 Text en © 2015 Mooney et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Mooney, Jason P.
Lee, Seung-Joo
Lokken, Kristen L.
Nanton, Minelva R.
Nuccio, Sean-Paul
McSorley, Stephen J.
Tsolis, Renée M.
Transient Loss of Protection Afforded by a Live Attenuated Non-typhoidal Salmonella Vaccine in Mice Co-infected with Malaria
title Transient Loss of Protection Afforded by a Live Attenuated Non-typhoidal Salmonella Vaccine in Mice Co-infected with Malaria
title_full Transient Loss of Protection Afforded by a Live Attenuated Non-typhoidal Salmonella Vaccine in Mice Co-infected with Malaria
title_fullStr Transient Loss of Protection Afforded by a Live Attenuated Non-typhoidal Salmonella Vaccine in Mice Co-infected with Malaria
title_full_unstemmed Transient Loss of Protection Afforded by a Live Attenuated Non-typhoidal Salmonella Vaccine in Mice Co-infected with Malaria
title_short Transient Loss of Protection Afforded by a Live Attenuated Non-typhoidal Salmonella Vaccine in Mice Co-infected with Malaria
title_sort transient loss of protection afforded by a live attenuated non-typhoidal salmonella vaccine in mice co-infected with malaria
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569369/
https://www.ncbi.nlm.nih.gov/pubmed/26366739
http://dx.doi.org/10.1371/journal.pntd.0004027
work_keys_str_mv AT mooneyjasonp transientlossofprotectionaffordedbyaliveattenuatednontyphoidalsalmonellavaccineinmicecoinfectedwithmalaria
AT leeseungjoo transientlossofprotectionaffordedbyaliveattenuatednontyphoidalsalmonellavaccineinmicecoinfectedwithmalaria
AT lokkenkristenl transientlossofprotectionaffordedbyaliveattenuatednontyphoidalsalmonellavaccineinmicecoinfectedwithmalaria
AT nantonminelvar transientlossofprotectionaffordedbyaliveattenuatednontyphoidalsalmonellavaccineinmicecoinfectedwithmalaria
AT nuccioseanpaul transientlossofprotectionaffordedbyaliveattenuatednontyphoidalsalmonellavaccineinmicecoinfectedwithmalaria
AT mcsorleystephenj transientlossofprotectionaffordedbyaliveattenuatednontyphoidalsalmonellavaccineinmicecoinfectedwithmalaria
AT tsolisreneem transientlossofprotectionaffordedbyaliveattenuatednontyphoidalsalmonellavaccineinmicecoinfectedwithmalaria